Institute for Neuroscience, University of Texas at Austin, TX, USA.
Restor Neurol Neurosci. 2013;31(1):87-97. doi: 10.3233/RNN-2012-120245.
Ceftriaxone, a β-lactam antibiotic, can selectively enhance the expression of glutamate transporter 1 (GLT1), the most abundant astrocytic glutamate transporter expressed in the cortex. It has been found to have neuroprotective effects when administered prior to brain ischemic damage or during the acute phase post-stroke, but its effects in chronic period have not been examined.
We examined the effects of ceftriaxone on the acquisition of motor skill and the functional outcome after focal ischemic cortical lesions. In adult male rats, ceftriaxone (200 mg/kg) or vehicle was intraperitoneally injected daily for 5 days, a treatment regime previously established to upregulate GLT-1. This preceded 28 days of skilled reach training in intact animals or began 3 days following lesions, followed by 5 weeks of rehabilitative reach training.
In intact rats, ceftriaxone did not affect skill learning rate or final performance. Following ischemic lesions, though there was no significant difference in lesion sizes between groups, ceftriaxone exacerbated initial deficits in reaching performance.
These findings of detrimental effects on motor functional outcome suggest that ceftriaxone may be more useful for neuroprotection during the acute phase of ischemia than for functional recovery in the post-acute period after ischemic damage.
头孢曲松是一种β-内酰胺类抗生素，可选择性增强谷氨酸转运体 1(GLT1)的表达，GLT1 是皮质中表达最丰富的星形胶质细胞谷氨酸转运体。研究发现，在脑缺血损伤前或中风后急性期给予头孢曲松具有神经保护作用，但尚未研究其在慢性期的作用。
我们研究了头孢曲松对获得运动技能和局灶性皮质缺血性损伤后功能结果的影响。在成年雄性大鼠中，头孢曲松（200mg/kg）或载体每天腹膜内注射 5 天，这一治疗方案先前已被证实可上调 GLT-1。这一方案在完整动物进行 28 天的熟练抓取训练之前或在损伤后 3 天开始，随后进行 5 周的康复抓取训练。
在完整大鼠中，头孢曲松不影响技能学习速度或最终表现。在缺血性损伤后，尽管各组之间的损伤大小没有显著差异，但头孢曲松加重了初始抓握表现的缺陷。
这些对运动功能结果产生不利影响的发现表明，头孢曲松在缺血的急性期对神经保护可能更有用，而在缺血损伤后的急性期后对功能恢复可能作用不大。
